The objective of this proposal is to learn how genes specify the structure of a simple sensory nervous system by studying the structural lesions found in chemotaxis defective mutants of the soil nematode Caenorhabditis elegans. This organism is ideal for genetic analysis of neural structure: it is small and easily cultured; many behavioral mutants have been obtained and genetically mapped; and the anatomy of its sensory nervous system has been completely reconstructed from serial section electronmicrographs. Its chemotactic behavior includes attraction to more than four classes of attractants, cyclic nucleotides, anions, cations, hydroxyl ions and undefined bacterial and fungal exudates. The nematode is also repelled by acid, zinc and aromatic compounds. Using the chemotactic response to remove normal animals, mutants defective in some or all of their responses to attractants have been selected already. Anatomical analysis of these mutants reveals specific and reproducible lesions in sensory neuron endings. More such mutants will be sought by selection against all classes of attractants. These will be characterized genetically, behaviorally and anatomically. By correlation of anatomical and behavioral defects the functions of each neuron may be assignable. By classification of the subsets of neurons affected by each mutation and the types of lesions found in these neurons it may be possible to recognize elements of structure specified by single genes, and to hypothesize the embryological or biochemical defects in some mutants. In order to test these hypothesis and to develop new ones, temperature sensitive mutants altered in fertilization will be sought. Sperm will be isolated from these mutants and characterized biochemically and immunologically.